Aberrant function of cell cycle regulators results in uncontrolled cell proliferation, making them attractive therapeutic targets in cancer treatment. Indeed, survival of many cancers exclusively ...relies on these proteins, and several specific inhibitors are in clinical use. Although the ubiquitin-proteasome system is responsible for the periodic quality control of cell cycle proteins during cell cycle progression, increasing evidence clearly demonstrates the intimate interaction between cell cycle regulation and selective autophagy, important homeostasis maintenance machinery. However, these studies have often led to divergent rather than unifying explanations due to complexity of the autophagy signaling network, the inconsistent functions between general autophagy and selective autophagy, and the different characteristics of autophagic substrates. In this review, we highlight current data illustrating the contradictory and important role of cell cycle proteins in regulating autophagy. We also focus on how selective autophagy acts as a central mechanism to maintain orderly DNA repair and genome integrity by degrading specific cell cycle proteins, regulating cell division, and promoting DNA damage repair. We further discuss the ways in which selective autophagy may impact the cell cycle regulators, since failure to appropriately remove these can interfere with cell death-related processes, including senescence and autophagy-related cell death. Imbalanced cell proliferation is typically utilized by cancer cells to acquire resistance. Finally, we discuss the possibility of a potent anticancer therapeutic strategy that targets selective autophagy or autophagy and cell cycle together.
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•Eco-friendly Silver nanoparticles were biosynthesized using a EPS from Lactobacillus brevis.•Biosynthesized silver nanoparticles are spherical with an average size of 45 nm.•AgNPs ...showed potent antimicrobial activity against Staphylococcus aureus and E. coli.•AgNPs exhibited excellent antioxidant activity against free radicals.•Newly biosynthesized silver nanoparticles have potential applications in various industries.
Recently, silver nanoparticles gain significant attention due to their applications in various fields. The aim of present study was to develop the eco-friendly, cost effective, and simple method to biosynthesized the silver nanoparticle using sliver nitrate as precursor. In this study, we investigated the physical characterization and biotechnological applications of biosynthesized silver nanoparticle using exopolysaccharide of probiotic Lactobacillus brevis MSR104 isolated from Chinese koumiss. Biosynthesized silver nanoparticles were characterized using the fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction analysis, and elemental analyzer. The achieved results indicate that silver nanoparticles varied in sized with an average size of 45 nm. The X-ray diffraction analysis results showed that the silver nanoparticles have a crystalline nature. The results of antimicrobial assay indicated that the silver nanoparticles exhibited outstanding antimicrobial activity in dose dependent manner against both Gram’s negative as well as Gram’s positive. The antioxidant results indicate that the silver nanoparticles showed excellent scavenging rate against DPPH free radicals (81.4 ± 1.2%) and nitric oxide free radicals (75.06 ± 0.4%). Furthermore, the results of MTT assay revealed that the AgNPs significantly reduced the percentage of live HT-29 cells at higher concentration. This study concluded that the newly synthesized silver nanoparticles have antibacterial, antioxidant, and anticancer applications in agricultural and food industries.
The p21-Activated kinase 1 (PAK1), a member of serine-threonine kinases family, was initially identified as an interactor of the Rho GTPases RAC1 and CDC42, which affect a wide range of processes ...associated with cell motility, survival, metabolism, cell cycle, proliferation, transformation, stress, inflammation, and gene expression. Recently, the PAK1 has emerged as a potential therapeutic target in cancer due to its role in many oncogenic signaling pathways. Many PAK1 inhibitors have been developed as potential preclinical agents for cancer therapy. Here, we provide an overview of essential roles that PAK1 plays in cancer, including its structure and autoactivation mechanism, its crucial function from onset to progression to metastasis, metabolism, immune escape and even drug resistance in cancer; endogenous regulators; and cancer-related pathways. We also summarize the reported PAK1 small-molecule inhibitors based on their structure types and their potential application in cancer. In addition, we provide overviews on current progress and future challenges of PAK1 in cancer, hoping to provide new ideas for the diagnosis and treatment of cancer.
Nanomedicine has become one of the most promising technologies to modernize the traditional food. However, not only the public perception of the new technology is uncertain, but also the regulators ...have not yet to agree on rules that apply globally. The gastrointestinal tract microbiota and its genes (the microbiome) are considered a fundamental part of the human body. The gut microbiota is a major part of the host microbiota and contains approximately 3 × 1013 bacterial cells in a commensal relationship with the host. However, once the gastric ecosystem is altered, various bacterial species (e.g., antibiotic-resistant Enterococcus and Clostridium difficile) can increase and develop pathogenic phenotypes. Recent evidence suggests that the gut microbiota is involved in carcinogenesis and can enhance the activity, efficacy, and toxicity of anticancer therapies. Recently, there is fast-growing concern regarding the effect of nanoparticles on the human gut microbiota. Nanomaterials can enter the human body via skin contact, ingestion, and inhalation.
In the present review, the recent advances on the roles of microbiota and nanomaterials in cancer therapy, the microbiota and their metabolic interventions via nanomaterials, microbial inspiration via nanomaterials, and the challenges associated with using nanomaterials in humans and animals is discussed. In short, this review will focus on the current status and future perspectives of gut microbiota targeted nanotechnology for cancer therapy and cancer-related metabolic diseases.
The changes in the gut microbiota or microbiome play vital roles in human diseases such as cancer. Traditional microbiome treatments have led to improved cancer treatments in some cases; however, problems such as collateral injury to the symbiotic microbiome and reliability of these treatment methods have led to new technological developments designed specifically for cancer microbiota crossing point. Hence, the prosperousness of nanomaterials in cancer prevention has led to the idea that nanomaterials can alter the cancer-causing microbiome/microbiota and their metabolites as well as alter the cancer microenvironment. Therefore, nanomaterials can be used as novel strategies to treat cancer. However, this emerging research area requires further in vivo clinical trials to determine the exact mechanisms of action involved in treating cancer via nanomaterials. Further studies should explore the connection between nanomaterials, the microbiota, microbial metabolites, cancer and cancer-related microenvironments in animals and humans.
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•Increasing evidence suggested that the gut microbiota dysbiosis influence cancer.•Interaction between nanomaterials and gut microbiota are largely unexplored.•The concept of nanomedicine based approached to alter gut microbiota for cancer therapy has been proposed.•The gut microbiota and nanomedicine might provide new specific biomarkers for cancer therapy.•Future perceptive toward the development of novel nanomedicine for cancer therapy are discussed.
ATAD2 has been reported to play an important role in the processes of numerous cancers and validated to be a potential therapeutic target. This work is to discover potent ATAD2 inhibitors and ...elucidate the underlying mechanisms in breast cancer. A novel ATAD2 bromodomain inhibitor (AM879) was discovered by combining structure-based virtual screening with biochemical analyses. AM879 presents potent inhibitory activity towards ATAD2 bromodomain (IC
50
= 3565 nM), presenting no inhibitory activity against BRD2-4. Moreover, AM879 inhibited MDA-MB-231 cells proliferation with IC
50
value of 2.43 µM, suppressed the expression of c-Myc, and induced significant apoptosis. Additionally, AM978 could induce autophagy via PI3K-AKT-mTOR signalling in MDA-MB-231 cells. This study demonstrates the development of potent ATAD2 inhibitors with novel scaffolds for breast cancer therapy.
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•MSR101 EPS from Lactobacillus kefiri is a heteropolymer of glucose and galactose.•The MSR101 EPS has a porous structure having plasticized film features.•The MSR101 EPS showed ...semi-crystalline nature with excellent thermal properties.•The MSR101 EPS induced apoptosis by up-regulating and down-regulating the apoptosis-related genes.
The exopolysaccharide (EPS) from Lactobacilli play a vital part in their probiotic action; on the other hand, up to date, there is little data exist about the effect of EPS on cancer. The aim of the current study is the EPS isolation produced by Lactobacillus kefiri MSR101 (MSR101 EPS) and examination of structural characteristics as well as their capability to prevent the colon cancer (HT-29) cells growth. For the first time, the structure of EPS from Lactobacillus kefiri MSR101 is identified, which is heteropolysaccharide with a repeating unit containing glucose and galactose. The FT-IR and NMR analysis of MSR101 EPS indicates the occurrence of carboxyl, hydroxyl groups, respectively. The XRD results indicated that the MSR101 EPS has partial crystalline nature. SEM and AFM micrographs revealed an extremely spongy structure which suggests that the MSR101 EPS has plasticized film features. Furthermore, the in-vitro anticancer activity results suggested that the newly isolated MSR101 EPS (400 µg/ml) had satisfactory anticancer action on HT-29 cancerous cells (44.1%) and up-regulate the expression of Cyto-c, BAX, BAD, caspase3, caspase8, and caspase9. In general, the present results suggested that the exopolysaccharide from Lactobacillus kefiri MSR101 not only used in the functional food product but also considered as a topical medication due to their effectiveness against colon cancer.
Modulation of autophagy has been increasingly regarded as a promising cancer therapeutic approach. In this study, we screened several ginsenosides extracted from Panax ginseng and identified ...ginsenoside Ro (Ro) as a novel autophagy inhibitor. Ro blocked the autophagosome-lysosome fusion process by raising lysosomal pH and attenuating lysosomal cathepsin activity, resulting in the accumulation of the autophagosome marker MAP1LC3B/LC3B and SQSTM1/p62 (sequestosome 1) in various esophageal cancer cell lines. More detailed studies demonstrated that Ro activated ESR2 (estrogen receptor 2), which led to the activation of NCF1/p47
PHOX
(neutrophil cytosolic factor 1), a subunit of NADPH oxidase, and subsequent reactive oxygen species (ROS) production. Treatment with siRNAs or inhibitors of the ESR2-NCF1-ROS axis, such as N-acetyl-L-cysteine (NAC), diphenyleneiodonium chloride (DPI), apocynin (ACN), Tiron, and Fulvestrant apparently decreased Ro-induced LC3B-II, GFP-LC3B puncta, and SQSTM1, indicating that ROS instigates autophagic flux inhibition triggered by Ro. More importantly, suppression of autophagy by Ro sensitized 5-fluorouracil (5-Fu)-induced cell death in chemoresistant esophageal cancer cells. 5-Fu induced prosurvival autophagy, and by inhibiting such autophagy, siRNAs against BECN1/beclin 1, ATG5, ATG7, and LC3B enhanced 5-Fu-induced autophagy-associated and apoptosis-independent cell death. We observed that Ro potentiates 5-Fu cytotoxicity via delaying CHEK1 (checkpoint kinase 1) degradation and downregulating DNA replication process, resulting in the delayed DNA repair and the accumulation of DNA damage. In summary, these data suggest that Ro is a novel autophagy inhibitor and could function as a potent anticancer agent in combination therapy to overcome chemoresistance.
High expression of glutaminyl cyclase (QC) contributes to the initiation of Alzheimer's disease (AD) by catalyzing the generation of neurotoxic pyroglutamate (pE)-modified β-amyloid (Aβ) peptides. ...Preventing the generation of pE-Aβs by QC inhibition has been suggested as a novel approach to a disease-modifying therapy for AD. In this work, a series of diphenyl conjugated imidazole derivatives (DPCIs) was rationally designed and synthesized. Analogues with this scaffold exhibited potent inhibitory activity against human QC (hQC) and good in vitro blood-brain barrier (BBB) permeability. Further assessments corroborated that the selected hQC inhibitor 28 inhibits the activity of hQC, dramatically reduces the generation of pE-Aβs in cultured cells and in vivo, and improves the behavior of AD mice.
•Acteoside from kudingcha showed inhibition of lipase activity.•Acteoside might act as a non-competitive pancreatic lipase inhibitor.•Acteoside altered the conformation of lipase, which changed the ...enzyme activity.
Acteoside is the most abundant and major active component of Ligustrum purpurascens (kudingcha tea). Here, we explored the anti-obesity properties of acteoside by investigating its effect on lipase activity. Characterization of acteoside and lipase by fluorescence spectroscopy, isothermal titration calorimetry and circular dichroism revealed that acteoside might act as a non-competitive lipase inhibitor. Acteoside bound to lipase at Ka=1.88×104lmol−1. Thermodynamic features suggested that the binding interaction was mainly hydrophobic and the complex was stabilized by hydrogen bonding, with 1:1 interaction of acteoside and lipase. Furthermore, docking results supported experimental findings and revealed hydrogen bonding with Lys271, Leu272 and Thr68 of lipase. This non-covalent bonding between acteoside and lipase alters the molecular conformation of lipase, which decreases the enzyme catalytic activity.
This study explores the antifungal properties of Agaricus blazei Murrill, a valuable medicinal and edible fungus. Six compounds (1–6) were first isolated from A. blazei using various isolation ...techniques and identified using spectroscopic methods. These compounds include linoleic acid, 1,1′-oxybis(2,4-di-tert-butylbenzene), glycerol monolinoleate, volemolide (17R)-17-methylincisterol, (24s)-ergosta-7-en-3-ol, and dibutyl phthalate. This study also assesses the antifungal activities of these compounds against Trichophyton mentagrophology, Trichophyton rubrum, Candida albicans, and Cryptococcus neoformans. The results demonstrate varied sensitivities against these pathogenic fungi, with compound 2 showing significant inhibition against T. mentagrophology, compound 3 showing significant inhibition against T. rubrum, and compound 6 showing significant inhibition against C. albicans. This study underscores the medicinal potential of A. blazei as an antifungal agent and sheds light on its valuable research implications.
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